Regulation of normal immunologic reactivity involves the balance between positive and negative influences exerted by various subsets of T cells. Abnormally hyperactive and hypoactive T cells are believed to be associated with several immune disorders, including AIDS (hypoactivity and destruction of the helper T cell subset), and a variety of autoimmune disorders, such as MHC-associated autoimmune disease (e.g. lupus erythematosus) which is believed to be caused by excessive production of gamma interferon by T cells.
T cells have been identified by certain phenotypic cell surface markers. For example, the surface molecule T8, which is present on human T cells of the cytotoxic subset, can be detected by immunofluorescent staining using murine anti-human monoclonal antibodies, such as OKT8 (Ortho Diagnostics, Raritan, NJ) or Leu-2 (Becton-Dickinson, Mountain View, CA). However, such markers are, at best, only useful in measuring the size of subpopulations, they do not necessarily imply that the cells are secreting products associated with an activated state.
Many diagnostic assays have been developed which are based on either immunochemical detection of proteins, e.g. U.S. Pat. Nos. 4,562,003; 4,474,892; and 4,427,782; or the detection of nucleic acids, either RNA or DNA, present in or produced by target cells, e.g. Pettersson et al., Immunology Today, Vol. 6, pgs. 268-272 (1985); Falkow et al., U.S. Pat. No. 4,358,535; and Gillespie et al., U.S. Pat. No. 4,483,920. The latter assays use nucleic acid probes, usually fluorescently labeled or radioactively labeled DNAs or RNAs, which can be preferentially hybridized to complementary target nucleic acids in appropriately prepared samples or tissues. The assays can take a variety of forms, e.g. RNA blotting: Thomas, Proc. Natl. Acad. Sci., Vol. 77, pgs. 5201-5205 (1980); dot hybridization: White et al., J. Biol. Chem., Vol. 257, pgs. 8569-8572 (1982); Southern blotting: Southern, J. Mol. Biol., Vol. 98, pgs. 503-517; and in situ hybridization: Pinkel et al., Proc. Natl. Acad. Sci., Vol. 83, pgs. 2934-2938 (1986); and Angerer et al., Genetic Engineering, Vol. 7, pgs. 43-65 (1985).
In view of the present lack of convenient direct methods for measuring abnormal T cell activation, the availability of sensitive immunochemical assays or nucleic acid probes for detecting activated T cells would provide useful diagnostic tools.